Removal of the adrenal glands from male rats causes significant depletion of zymogen granulation of the pancreas. The female rat does not demonstrate these changes following adrenalectomy. However, if the ovaries are removed in addition to the adrenal glands, alterations similar to those observed in the pancreas of the adrenalectomized male become apparent. Treatment of the male adrenalectomized rat, or female adrenalectomized-ovarectomized rat, with estradiol or triamcinolone (glucocorticoid) reverts the pancreas to normal appearance within 9 hours. Repletion of zymogen granulation and accumulation of protein in the presence of these steroids results from the net effects of diminished protein synthesis and decreased protein secretion. Thus, a simulataneous, but unbalanced reduction of both protein synthesis and protein secretion leads to accumulation of protein within the prancreas. Since inhibition of protein synthesis by triamcinolone occurs prior to protein accumulation, it is possible that this sterioid inhibits, initially, the synthesis of specific proteins required for the secretory process. The major objectives of this research program are to determine: whether triamcinolone (or estradiol) act directly on the pancreas; whether secretion of zymogens is controlled by steroids under physiological conditions; whether triamcinolone and estradiol interact at the same or separate sites; and whether zymogen secretion can occur from the cytosol and bypass the exocytotic pathway.